Urinary levels of kallikrein and kallistatin in pregnancy-induced hypertension

Paolo Madeddu, Julie Chao, Lee Chao, Mirella Soregaroli, Adriana Valcamonico, Luca Valsecchi, Nicola Glorioso, Tiziana Frusca

Research output: Contribution to journalArticle

Abstract

Objective: We evaluated if urinary excretion of kallikrein and kallistatin (a glandular kallikrein inhibitor) is altered early during gestation in patients who will ultimately develop pregnancy-induced hypertension. Methods: The protocol was designed as a nested, longitudinal case-control study. Overnight urine collections were obtained at 12-20, 24-26, and 30-32 weeks of gestation in a consecutive series of 350 primigravidae. Urinary kallikrein (amidolytic assay) and kallistatin (enzyme-linked immunosorbent assay) levels were measured in all patients (n == 24) who were found to be affected by pregnancy-induced hypertension. In addition, urinary kallikrein and kallistatin levels were measured in 24 women used as controls. They were chosen from the group of 326 normotensive subjects by matching them with the hypertensive patients for age and gestational time at the occasion of urine collections. Results: Prevalence of pregnancy-induced hypertension with or without proteinuria was 2.3% and 4.6% respectively. Onset of hypertension was similar in the two groups. Among patients with pregnancy-induced hypertension without proteinuria, urinary kallikrein excretion was depressed since early phases of gestation only in those subjects whose plasma levels of uric acid were above the confidence limits of normal distribution. In the group of women affected by pregnancy-induced hypertension with proteinuria, kallikrein excretion did not differ from that found in controls; however, inactive/active kallikrein ratio was greater. Urinary kallistatin levels were higher in the latter group compared with controls at 24-26 but not at 30-32 weeks. A positive correlation was found between urinary kallistatin and inactive kallikrein levels. Conclusions: Alterations in urinary kallikrein excretion are present in pregnant women with pregnancy-induced hypertension without proteinuria but with elevated plasma uric acid levels, while excessive excretion of kallistatin occurs in patients with pregnancy-induced hypertension with proteinuria. Though these abnormalities might play a role in the pathogenesis of gestational hypertension, some cautiousness is necessary before recommending a systematic evaluation of the kallikrein-kallistatin system as a screening test on the general population.

Original languageEnglish
Pages (from-to)201-212
Number of pages12
JournalHypertension in Pregnancy
Volume14
Issue number2
DOIs
Publication statusPublished - 1995

Keywords

  • Hypertension
  • Kallikrein
  • Kinins
  • Pregnancy

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Internal Medicine

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    Madeddu, P., Chao, J., Chao, L., Soregaroli, M., Valcamonico, A., Valsecchi, L., Glorioso, N., & Frusca, T. (1995). Urinary levels of kallikrein and kallistatin in pregnancy-induced hypertension. Hypertension in Pregnancy, 14(2), 201-212. https://doi.org/10.3109/10641959509009581